ABSTRACT ? BIOSPECIMEN/PATHOLOGY CORE The overarching goal of this SPORE is to understand the biological underpinnings of hyperactivated p21ras pathway signals in the pathogenesis of childhood malignancies of neurofibromatosis type 1 and to bring new therapies to the clinic. Each project explores this theme using a different disease model. However, all projects interweave human, mouse and in vitro studies to identify factors that modify the effects of Ras. To ensure the success of these studies, complementary cutting-edge technologies will be used to address key questions related to disease susceptibility, likelihood of disease relapse, and risk for other malignancies. The Biospecimen and Pathology Core will receive human and mouse samples from all four projects in the SPORE. The core will also provide pathological review of all samples and will make these data available to all SPORE investigators and the broader research community. The specific aims of this core are: Aim 1: Utilize uniform biospecimen collection, processing, tracking and distribution procedures for samples collected as part of SPORE projects. Aim 2: Apply uniform pathology protocols for the characterization of animal and human samples collected as part of SPORE projects. Aim 3: Develop and maintain a study registration database that contains key clinical, diagnostic, pathological and sample information.